| Objective:The study was aimed at exploring the correlation between Epstein-Barr virus (EBV) infection and Hodgkin’s lymphoma (HL) in Uygur nationality of Xinjiang area through the detection EBV in HL patients tissues,and qualitative and quantitative investigation of EBV-DNA in their peripheral blood.On the basis of that, further research was carried out on the correlation between high resolution allelic genes of human leukocyte antigen-A (HLA-A) and EBV positive HL in Uygur nationality, in order to explore the interaction of HLA-A genetype and EBV in a high incidence HL in Uygur nationality of Xinjiang.Methods:1)40cases of HL in Uygur nationality and20cases of reactive lymphoid hyperplasia (RLH) by using in situ hybridization (ISH) were employed to detect the EBV-encoded small RNA (EBER) in these tissues. And then test was conducted on the expressions of latent membrane protein-2A(LMP-2A) in HL with EBER positive cases by using the method of immunohistochemistry(IHC).2) In addition,preliminary qualitative detection was carried out on the infection status of45cases of HL patients in Uygur nationality and110cases of healthy people in the same nationality of EBV-DNA peripheral blood by using nested PCR. And then EBV viral load was assessed respectively on the two groups in terms of positive EBV-DNA peripheral blood by using nested PCR and fluorescent quantitative-PCR (FQ-PCR),so as to analyze the correlation between the load level of EBV-DNA and clinical pathological factors.3) By using the method of sequence based typing (SBT),comparison were analyzed in terms of the distribution frequency of high resolution allelic genes of HLA-A on the above HL patients and healthy people.Results:1)Twenty-six cases of40Hodgkin’s lymphomas were showed EBER positive (65.0%). The positive rate in lymphoid reactive hyperplasia cases was25.0%(5/20).The difference was found between two groups (P<0.05).The expression level of EBER was no difference among each group about gender,clinical stage, pathological types and tumor bulk(P>0.05).Most of HL patients with B symptoms had EBV infection(P<0.05).Among HL patients with EBV infection in the Uygur nationality, the expression rate of LMP-2A protein positive rate is57.7%(15/26).The research found out that expression of LMP-2A protein was only existed in the hypotype of mixed cellularity (MC) and hypotype of nodular sclerosis (NS), while there was no LMP-2A protein expression in RLH group with EBV infection.The positive expression of LMP-2A was often found in EBV positive HL patients With B symptoms (P<0.01).2)The detection rate of peripheral blood EBV-DNA of HL patients in the Uygur nationality was53.3%(24/45) while the rate of healthy people was26.4%(29/110),which also had statistical difference (P=0.001).Among two groups of EBV-DNA positive patients, the quantitative detection of HL patients and healthy people had no statistical difference (P=0.490).The EBV-DNA load levels of patients whose ages were less than10years or more than35years were lower than those between10to20(P=0.025).The EBV-DNA load levels of patients who were in III+IV stage were higher than those in Ⅰ+Ⅱ stage (P=0.013).The EBV-DNA load levels of patients with B symptoms were higher than those who had no symptoms (P=0.020).3)Furthermore,32different HLA-A alleles had been detected from HL patients in Uygur nationality in this research, while44different HLA-A alleles had been detected from the healthy group.The distribution frequency of HLA-A high resolution allelotypes satisfied the Hardy-Weinberg genetic balance test (P=0.61).The frequencies of HLA-A*01:01:01:01, A*03:01, A*01:01, A*02:07allele were significantly higher than those in control groups (45.48%VS16.04%,39.68%VS18.35%,33.91%VS18.35%,28.18%VS13.73%,P<0.01), while the frequencies of HLA-A*02:01, A*11:01alleles were significantly lower (69.05%VS85.47%,16.81%VS32.34%,P<0.01).The most frequent antigens were A2in two groups (21.11%;21.82%).There were no significantly different about HLA-A antigen types between HL patients and normal people (P>0.05).By the observation of the data,we could see the following trend that the percentage of HLA-A1antigenic type in EBV positive HL patients was increased while that of HLA-A2antigenic type in EBV positive HL patients was decreased.The percentage of HLA-A1, All, A23antigenic type in EBV negative HL patients was decreased.In addition,there were not difference in the rate of HLA-A*02:01and HLA-A*01:01genotype between patients and healthy EBV-positive controls, while the EBV positive expression rate of HL patients with HLA-A*11:01:01allelic genes was higher than that of the healthy people with this kind of genetype (P=0.038).Conclusions:1)EBV infection rate of HL patients in Uygur nationality was higher, which indicated that there was a certain correlation between EBV infection and HL of Uygur nationality.2)The qualitative detection of the infection status of peripheral blood EBV-DNA had the same result as that in the EBER of the tumor tissue.The peripheral blood EBV-DNA load level of HL patients might reflect the degree of tumor invasion of HL patients in some level. The detection of EBV infection, whether in the tissue of HL patients or in peripheral blood,might indicate unfavorable prognosis.lt is nessary for us to prove in future follow-up.3)But the function of the simple EBV infection participated in HL of Uygur nationality was limited.The research showed that some genetic susceptibility genes or antagonistic genes might participate in the high occurrence of HL in Uygur nationality. The research showed that the genetype of HLA-A*01:01:01:01, A*03:01, A*01:01and A*02:07might be the genetic susceptibility genes of HL in Uygur patients, while HLA-A*02:01and A*11:01may be the protective genes.HLA-A*11:01:01gene might be susceptibility genes of EBV positive HL. The data showed the trends,which suggested that HLA-A1antigen type may be susceptibility gene of EBV positive HL, HLA-A2antigen type be protective genes of EBV positive HL.HLA-A1,A11,A23antigen type may be protective genes of EBV negative HL. |
PDF Full Text Request